Prion diseases are fatal neurodegenerative disorders caused by the deposition of scrapie prion protein aggregates (PrP^Sc) in the brain. We previously reported that styrylchromone (SC) and benzofuran (BF) derivatives have potential as imaging probes for PrP^Sc. To further improve their properties, we designed and synthesized 2-(benzofuran-2-yl)-chromone (BFC) derivatives hybridized with SC and BF backbones as novel single-photon emission computed tomography probes for the detection of cerebral PrP^Sc deposits. Recombinant mouse prion protein (rMoPrP) aggregates and mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice were used to evaluate the binding properties of BFC derivatives to PrP^Sc. The BFC derivatives exhibited high binding affinities (equilibrium dissociation constant [K_d] = 22.6–47.7 nM) for rMoPrP aggregates. All BFC derivatives showed remarkable selectivity against amyloid beta aggregates. Fluorescence microscopy confirmed that the fluorescence signals of the BFC derivatives corresponded to the antibody-positive deposits of PrP^Sc in mBSE-infected mouse brains. Among the BFC derivatives, [¹²⁵I]BFC–OMe and [¹²⁵I]BFC–NH₂ exhibited high brain uptake and favorable washout from the mouse brain. In vitro autoradiography demonstrated that the distribution of [¹²⁵I]BFC–OMe in the brain tissues of mBSE-infected mice was colocalized with PrP^Sc deposits. Taken together, BFC derivatives appear to be promising prion imaging probes.

中文翻译：

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新型 2-(Benzofuran-2-yl)-chromone 衍生物的合成和生物学评价，用于大脑中朊病毒沉积物的体内成像

^{朊病毒病是由痒病朊病毒蛋白聚集体 (PrP Sc} ) 在大脑中沉积引起的致命性神经退行性疾病。我们之前报道过，苯乙烯基色酮 (SC) 和苯并呋喃 (BF) 衍生物具有作为 PrP ^Sc成像探针的潜力。为了进一步改善它们的特性，我们设计并合成了与 SC 和 BF 骨架杂交的 2-(benzofuran-2-yl)-chromone (BFC) 衍生物作为新型单光子发射计算机断层扫描探针，用于检测脑 PrP ^Sc沉积物。重组小鼠朊病毒蛋白 (rMoPrP) 聚集体和小鼠适应性牛海绵状脑病 (mBSE) 感染小鼠用于评估 BFC 衍生物与 PrP ^{Sc的结合特性}. BFC 衍生物对 rMoPrP 聚集体表现出高结合亲和力（平衡解离常数 [ K _d ] = 22.6–47.7 nM）。所有 BFC 衍生物都显示出对淀粉样蛋白 β 聚集体的显着选择性。荧光显微镜证实，BFC 衍生物的荧光信号对应于感染 mBSE 的小鼠大脑中 PrP ^{Sc的抗体阳性沉积物。}在 BFC 衍生物中，[ ¹²⁵ I]BFC-OMe 和 [ ¹²⁵ I]BFC-NH ₂表现出高脑摄取和从小鼠脑中有利的洗脱。体外放射自显影表明，[ ¹²⁵ I]BFC-OMe 在 mBSE 感染小鼠脑组织中的分布与 PrP 共定位^SC存款。总之，BFC 衍生物似乎是有前途的朊病毒成像探针。